Document Detail


Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer.
MedLine Citation:
PMID:  21423660     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative breast cancer (TNBC).
METHODS: TNBC cells were pretreated with Noscapine or Doxorubicin or combination and combination index values were calculated using isobolographic method. Apoptosis was assessed by TUNEL staining. Female athymic Nu/nu mice were xenografted with MDA-MB-231 cells and the efficacy of Noscapine, Doxorubicin and combination was determined. Protein expression, immunohistochemical staining were evaluated in harvested tumor tissues.
RESULTS: Noscapine inhibited growth of MDA-MB-231 and MDA-MB-468 cells with the IC(50) values of 36.16±3.76 and 42.7±4.3 µM respectively. The CI values (<0.59) were suggestive of strong synergistic interaction between Noscapine and Doxorubicin and combination treatment showed significant increase in apoptotic cells. Noscapine showed dose dependent reduction in the tumor volumes at a dose of 150-550 mg/kg/day compared to controls. Noscapine (300 mg/kg), Doxorubicin (1.5 mg/kg) and combination treatment reduced tumor volume by 39.4±5.8, 34.2±5.7 and 82.9±4.5 percent respectively and showed decreased expression of NF-KB pathway proteins, VEGF, cell survival, and increased expression of apoptotic and growth inhibitory proteins compared to single-agent treatment and control groups.
CONCLUSIONS: Noscapine potentiated the anticancer activity of Doxorubicin in a synergistic manner against TNBC tumors via inactivation of NF-KB and anti-angiogenic pathways while stimulating apoptosis. These findings suggest potential benefit for use of oral Noscapine and Doxorubicin combination therapy for treatment of more aggressive TNBC.
Authors:
Mahavir B Chougule; Apurva R Patel; Tanise Jackson; Mandip Singh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-15
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-22     Completed Date:  2011-07-05     Revised Date:  2013-07-19    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e17733     Citation Subset:  IM    
Affiliation:
College of Pharmacy, University of Hawaii, Hilo, Hawaii, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inducing Agents / metabolism
Animals
Antineoplastic Agents / pharmacology,  therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / pharmacology,  therapeutic use*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Breast Neoplasms / blood supply,  drug therapy*,  enzymology,  pathology
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA Fragmentation / drug effects
Doxorubicin / pharmacology,  therapeutic use*
Drug Synergism
Female
Humans
Immunohistochemistry
Mice
NF-kappa B / metabolism
Neovascularization, Pathologic / drug therapy,  pathology
Noscapine / pharmacology,  therapeutic use*
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
5S06GM008111-36/GM/NIGMS NIH HHS; G12 RR003020/RR/NCRR NIH HHS; G12 RR003020-26/RR/NCRR NIH HHS; G12 RR003020-27/RR/NCRR NIH HHS; G12RR03020-11/RR/NCRR NIH HHS; S06 GM008111-36/GM/NIGMS NIH HHS; SC1 CA161676/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/NF-kappa B; 128-62-1/Noscapine; 23214-92-8/Doxorubicin; EC 3.4.22.-/Caspase 3
Comments/Corrections

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